Official Title

Summary:

Neuroendocrine tumours (NETs) are rare, slow growing, and diagnosis is often delayed with
advanced metastases at presentation. In select patient populations, radioisotope therapy with
Lutetium-177 (Lu-DOTA-TATE) has been shown to be a safe and effective palliative therapy, and
has been widely used by research groups in Europe. Lu-DOTA-TATE has been used at the Cross
Cancer Institute to treat more than 200 patients with NETs since August, 2010. This study is
being done because the Lu-DOTA-TATE treatment was initially given under Health Canada's
Special Access Programme (SAP), with each individual treatment requiring separate approval.
Health Canada requested that the investigators conduct a clinical trial with Lu-DOTA-TATE,
with the goal of receiving approval to use Lu-DOTA-TATE as a marketed treatment agent.
The purpose of this study is to: 1) assess the efficacy of Lu-DOTA-TATE treatment in patients
with somatostatin receptor positive tumours; 2) and assess the safety of Lu-DOTA-TATE.

Trial Description

Primary Outcome:

Change in Tumour response (modified RECIST criteria, CT/MRI or Lu-177 scan) of the target lesion through end of treatment

Progression-free survival

Lu-177 scan disease evaluation

Change in tumour marker levels

Secondary Outcome:

Number of participants with adverse events as a measure of safety and tolerability

The proposed clinical trial will be a Phase II, open label, single site study in subjects
with somatostatin receptor positive tumours. Radioactive Lu-DOTA-TATE doses are fixed within
a range of 1.85

5.55 GBq ± 10%, with individual doses based on specified risk factors.
There will be two groups of subjects enrolled in this study. Group A subjects (primary
therapy) will have somatostatin receptor positive tumours and have never received
Lu-DOTA-TATE. Group B subjects (maintenance therapy) will be those subjects who have
previously received Lu-DOTA-TATE under the Special Access Programme (SAP) and will maintain
their treatment schedule when they are entered into the study.
All subjects in Group A will be treated in an induction stage using 10-14 week dosing for up
to 4 treatments. If an individual patient shows stable or improving disease status with no
significant toxicities after the 4 induction treatments, they will be assessed 12-20 weeks
after the last therapeutic treatment for entry into the maintenance stage. Patients will be
re-assessed for stable or improving disease status with no significant toxicities 12-20 weeks
after the last treatment of each cycle (1 cycle = 2 treatments at 22-40 week intervals) of
the maintenance stage for consideration of further maintenance cycles (re-evaluations), up to
a maximum of 4 cycles per patient if there have been no significant toxicities or
progression. At each treatment, an amino acid solution is infused prior to and during the
Lu-DOTA-TATE infusion to protect the kidneys. Subjects will be followed for 6 months and 1
year (± 4 weeks) following their last treatment dose to determine progression-free survival.
All subjects meeting evaluation criteria will be analysed for safety, and all Group A
subjects who have received at least two treatments of Lu-DOTA-TATE will be evaluated for
efficacy (progression free survival and effect on Quality of Life). Those Group B subjects
with adequate baseline data for comparison collected retrospectively from a chart review
study (REV-LUT-001) may also be evaluated for safety and efficacy. Additional optional
characterization of tumour samples from subjects who have had surgery before or during the
study may be performed to characterize NET tumour biology changes following Lu-DOTA-TATE
treatment.